The purpose of this proposal is to elucidate some of the parameters responsible for the generation of the mixed lymphocyte reaction (MLR) and production of killer T cells. We will focus on two broad areas: A) Biochemical and biodynamic properties of cell membranes of normal and neoplastic cells with varying capacity to act as stimulator cells. Cells will be labelled with radioisotopes and analyzed by biochemical and serological procedures. Turnover, shedding and capping of membrane antigens and total membrane proteins will be assessed for different stimulator cell populations. Cell surfaces will be modified with enzymes, glutaraldehyde or specifically by serological removal of antigens. Recovery will be blocked by inhibition of protein synthesis and modified cells will be used as stimulator cells. B) Immunobiological parameters of the response. 1) determinations of whether pure "LD" differences can promote generation of killer cells to a third party cell. 2) monolayer absorption of responding cells reacting to SD determinants. 3) isolation of subsets of B cells or tumor cells with differential immunogenicity. 4) discrimination between suppression versus non stimulation as a cause of poor immunogenicity. 5) role of anti-idiotype recognition or activation of stimulator cells through interaction with responder cells as a form of "back recognition". These studies will employ the allotype suppression system as a model. 6) analysis of the role of responder cell interactions using antisera to T cell differentiation antigens such as the LY series. 7) search for functional homologies of K and D region gene products of the major histocompatibility locus, particularly the T/t and TLA loci. Major methods include: mixed lymphocyte cultures, cell-mediated cytotoxicity (51Cr assay), velocity sedimentation, monolayer absorption, external and biosyntheic radiolabelling of cells, biochemical and serological analyses of membrane proteins.